This phase I/II trial is studying the side effects and best dose of flavopiridol and to see how well it works in treating patients with lymphoma or multiple myeloma. Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Dose limiting toxicity (DLT) for an individual disease group is defined as 1) any grade 3-4 non-hematologic toxicity (except leukopenia or neutropenia) that does not resolve or decrease to grade 1-2 within 2 weeks, or 2) any grade 4 hematologic toxicity that causes more than a 1 week delay in administration of therapy. The maximum tolerated dose (MTD) is defined as that dose level beneath the dose at which 2 or more of 6 patients experience DLT.

Complete and partial response rate (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Qualitative and quantitative toxicities in regard to organ specificity, time course, predictability, and reversibility as measured by CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]

Lymphoid/plasma cell malignancies [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetics of flavopiridol [ Time Frame: Days 1 and 22 ] [ Designated as safety issue: No ]

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

Drug: alvocidib

Given IV

Other Names:

FLAVO

flavopiridol

HMR 1275

L-868275

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the disease-specific dose-limiting toxicity and maximum tolerated dose of flavopiridol in patients with relapsed or refractory lymphoma or multiple myeloma.

III. Determine the qualitative and quantitative toxic effects or this drug, in terms of organ specificity, time course, predictability, and reversibility in these patients.

IV. Determine subsets of lymphoid/plasma cell malignancies that are suitable for larger phase II studies designed to further evaluate the efficacy and toxicity of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of this drug in these patients. II. Determine the effect of this drug on innate immunity (including T-, B-, and NK-cell subsets) and quantitative immunoglobulin levels in these patients.

OUTLINE: This is a phase I, dose-escalation study followed by a multicenter, phase II, pilot study. Patients enrolled in the phase II portion of the study are stratified according to diagnosis.

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

NOTE: The phase II treatment dose and schedule for hairy cell leukemia patients will be adapted from that developed in previous phase II studies of flavopiridol for the treatment of chronic lymphocytic leukemia.

After completion of study therapy, patients are followed every 3 months for 2 years.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosis of 1 of the following hematologic malignancies:

Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL)

Multiple myeloma

Patients in the phase II portion of the study are enrolled in 1 of the following strata according to diagnosis*

Patients with multiple myeloma must have detectable serum or urinary paraprotein

Patients with only cutaneous or subcutaneous disease (i.e., no measurable lymph node or bone marrow disease) are eligible if the extent of rash or skin involvement OR the size of the nodules are measurable

Must have received ≥ 1 prior therapy

Steroids alone are not considered prior therapy for patients with NHL or Hodgkin's lymphoma

High-dose dexamethasone is considered 1 prior therapy for patients with multiple myeloma

No standard effective therapy exists

No HIV-associated lymphoma

No nonsecretory multiple myeloma

Performance status - ECOG 0-2

No concurrent hormonal therapy except steroids for new adrenal failure or hormones administered for non-disease-related conditions (e.g., insulin for diabetes)

Hemoglobin ≥ 9.0 g/dL*

Absolute neutrophil count ≥ 1,500/mm^3*

Platelet count ≥ 50,000/mm^3*

AST ≤ 3 times upper limit of normal (ULN)

Bilirubin ≤ 2 times ULN

No major renal dysfunction that would preclude study compliance or participation

Phase I:

Creatinine ≤ 1.5 mg/dL

Creatinine clearance ≥ 70 mL/min

Phase II:

Creatinine ≤ 2.0 mg/dL

Creatinine clearance ≥ 50 mL/min

No cardiac or vascular dysfunction that would preclude central venous access, vigorous hydration, or hemodialysis

No other major cardiac dysfunction that would preclude study compliance or participation

No major pulmonary dysfunction that would preclude study compliance or participation

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception

No chronic gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) that would preclude study compliance or participation

No other major organ system (including neurological or psychiatric) dysfunction that would preclude study compliance or participation

Prior radiotherapy, including radioimmunotherapy, allowed

No concurrent radiotherapy

Prior idiotype vaccination or stem cell transplantation allowed

More than 6 weeks since prior mitomycin or nitrosoureas

No other concurrent chemotherapy

More than 4 weeks since other prior therapy

Prior systemic steroids allowed

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112723